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H5N1 Familial Cluster In Turkey Raises Pandemic Concerns
Recombinomics Commentary
January 4, 2006
The confirmation of H5N1 in the familial cluster of four significantly raises pandemic concerns. Media reports indicate H5N1 has been confirmed in two or three of the four siblings, but if all four developed pneumonia and bleeding gums, then all four almost certainly have H5N1 and will test positive in lab tests if proper samples are collected and handled properly.
Media reports indicate all four siblings developed symptoms about two days after eating a bird that had died. Transmission of H5N1 to four family members is unusually efficient. The largest confirmed familial cluster is a family of five from Haiphong in March of 2005. However, in that cluster the family members had mild symptoms and all recovered after a brief hospital stay.
The current cluster in Turkey is more severe. One boy has died and his two sisters are in critical condition. These cases likely have broader treatment options because the H5N1 linked to migratory birds have been sensitive to the amantadines, so combination treatment using and amantadine such as Symmetrel or Flumadine (ion channel blockers) and a neuramindase inhibitor (like Tamiflu or Relenza).
Reports of hospitalization of 11 additional cases from the same small town are cause for concern. Initial media reports indicated the unrelated patients had similar symptoms. If they had high fever, bleeding gums, and pneumonia, H5N1 infections are likely since many or most of the additional cases also reported either eating chicken prior to falling ill or being associated with dying poultry.
H5N1 in Europe is recombining. The recent report from Russia indicated all of the H5N1 isolates had a similar genetic composition related to the isolates from wild birds at Qinghai Lake. They all also hade the HA cleave site, GERRRKKR. However, isolates from the Crimea peninsula had the above sequence as well as RERRRKKR, the most common HA cleavage site in HPAI H5N1 in Asia. These data suggest the H5N1 is now recombining with other H5N1 strains.
However, the possibility of recombining with H9N2 is also quite real. H9N2 has become endemic in the Middle East and recombination between H5N1 and H9N2 could create the S227N polymorphism, which is associated with increased binding for human receptors and decreased binding for avian receptors. Acquisition of the S227N polymorphism would likely lead to more efficient human-to-human transmission.
Thus, the large familial cluster, combined with the additional patients admitted to the hospital in Van is cause for concern.
More information on the clinical status of the additional patients as well as the sequence of the H5N1 in the familial cluster would be useful.
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